Abstract

Differences in tea drinking habits are likely to vary by populations and
could contribute to the inconsistencies found between studies comparing
tea consumption and cancer risk. A population-based case-control study
was used to evaluate how usual tea consumption patterns of an older
population (n = 450) varied with history of
squamous cell carcinoma (SCC) of the skin. A detailed tea questionnaire
was developed to assess specific tea preparation methods and patterns
of drinking. In this southwestern United States population, black tea
was the predominant variety of tea consumed. We found no association
between the broad definition of any tea consumption and skin SCC.
However, the adjusted odds ratios (ORs) for hot and iced black tea
intake were 0.63 [95% confidence interval (CI), 0.36–1.10] and 1.02
(95% CI, 0.64–1.63), respectively. Controls were more likely to
report usually drinking strong hot tea (OR, 0.74; 95% CI, 0.53–1.03)
with increased brewing time (P for trend = 0.03).
Adjusting for brewing time, the association between skin SCC and hot
black tea consumption suggests a significantly lower risk in consumers
of hot tea compared to nonconsumers (OR, 0.33; 95% CI, 0.12–0.87).
This is one of the first studies to explore the relation between
different types of tea consumption and occurrence of human cancers. Our
results show that tea concentration (strength), brewing time, and
beverage temperature have major influences on the potential protective
effects of hot black tea in relation to skin SCC. Further studies with
increased sample sizes are needed to evaluate the interrelationships
between preparation techniques, tea type, and other life-style factors.

Introduction

Tea is one of the most ancient and widely consumed liquids in the
world. Tea leaves are primarily manufactured as green or black or
oolong, with black tea representing ∼80% of the tea products
consumed. Tea is known to have various clinical merits
(1)
, with recent laboratory studies demonstrating
inhibition of tumorigenesis in different animal models by tea and tea
polyphenols. The most extensively studied system is the mouse skin
tumorigenesis model with UV light (2)
. In contrast to the
consistent observations in animal models (3, 4, 5, 6, 7, 8, 9)
, the
effect of tea consumption on human cancers is not conclusive
(10)
. Some epidemiological studies have suggested a
potentially protective effect of black or green tea consumption against
human cancers of the lung (11, 12)
, breast
(13)
, colon and rectum (14)
, and prostate
(15)
. However, lack of specific information on the type of
tea consumed (e.g., black or green), amount and duration of
use, or method of preparation (e.g., hot or iced, strong or
weak) has limited all studies. Differences in the types of tea consumed
and tea drinking habits are likely to vary by populations and could
contribute to the inconsistencies between studies.

Although experimental studies have demonstrated inhibitory effects of
tea infusions and tea polyphenols on skin carcinogenesis, no studies
have examined the association between tea consumption and skin
SCC3
in humans. Furthermore, no studies have explored the potential for
differential effects between tea preparation techniques and cancer
risk.

The present study was designed to determine the usual tea consumption
patterns of an older southwestern United States population and to then
evaluate the association between tea consumption and risk of SCC of the
skin. A detailed TQ was developed to assess specific tea preparation
methods and patterns of drinking. This questionnaire was used in a
subgroup of subjects who participated in a population-based
case-control study of the potential relationships between environmental
risk factors and SCC occurrence.

Subjects and Methods

Study Population.

Cases of SCC of the skin were randomly selected from persons identified
through the Southeastern Arizona Skin Cancer Registry (16)
as a first occurrence of SCC. Cases were eligible if they were ≥30
years of age, had a histopathologically confirmed SCC of the skin
diagnosed within 4 months before the first interview, and had no prior
history of a skin cancer. Only non-Hispanic (Anglo) and Hispanic white
cases were eligible. Physician approvals were obtained to contact
identified cases. A study interviewer contacted the person by phone to
determine eligibility and invite participation. Over 83% of the cases
selected from the registry were interviewed for eligibility. Of the 531
eligible, 404 (76%) participated in the baseline study.
Population-based controls were selected using random-digit dialing
techniques. Phone numbers were randomly generated from the first four
digits of the cases’ residential telephone numbers. Controls were
frequency-matched to the cases by a 10-year age category and gender,
with one control per household invited to participate using modified
Waksburg criteria (17)
. Control subjects were eligible if
they had no history of any cancer within the past 5 years and met the
age, gender, and ethnicity groupings. A total of 1641 persons were
interviewed for eligibility; of these, 795 were eligible and 391 (49%)
completed baseline interview.

Between January 1993 and December 1996, 404 cases and 391controls were
recruited to baseline study. Sixty % of these subjects
(n = 566) provided complete dietary data and
constituted the population for this present study of tea consumption.
These individuals were recontacted by telephone between February 1998
and November 1998. A total of 466 (86%) individuals completed
the TQ (24 subjects were deceased, and 76 subjects could not be located
or refused a second interview).

All participants completed a structured interview detailing personal,
behavioral, and demographic characteristics. Information included: skin
characteristics, sunburns and tanning history, use of suntan lotions
and sunscreens, residential history, UV exposure during past year,
family history of skin cancer, past medical history, tobacco and
alcohol use, physical characteristics, and demographic information.
Daily mean nutrient intakes were calculated using the Minnesota
Nutrition Data System (version 2.9, Nutrition Coordinating Center,
University of Minnesota). Interviews were conducted by trained,
experienced interviewers. One interviewer conducted >90% of the
personal interviews and 100% of the dietary recalls and TQs. After
each interview, questionnaires were reviewed for completeness and
coded. Data entry was through screen-based entry programs that included
range checks.

TQ.

The TQ asked about usual tea intake over the past year, as well as a
lifetime consumption pattern and how the past year intake differed from
the lifetime pattern. Detailed information was sought for the past
year’s tea intake for each type of tea consumed (black, green, or
herbal and hot or iced). Information was sought for use of regular or
decaffeinated tea products and the usual brewing strength (weak,
medium, or strong). Usual or typical recipes for tea preparation were
obtained, e.g., number of tea bags/cup and brewing time.
This questionnaire was evaluated for short- (1 week) and long-term (6
month) reliability within a randomly selected sample of men and women
from the original case-control study who had not completed the 24-h
dietary recalls (n = 40). The correlation coefficients
between baseline and 6-month interviews were highly significant.

Data Analyses.

Distribution of demographic characteristics and potential risk factors
were compared between cases and controls using t tests for
continuous variables and χ2 tests for
categorical variables. χ2 tests for trend were
also calculated. Crude ORs and 95% CIs were calculated using the
non-tea drinkers as the reference category. Adjusted ORs were
calculated using multiple logistic regression with the initial models,
including age, sex, and energy intake. Potential confounding effects
were assessed for education, mean percent of kcal as fat; alcohol
intake (mean alcohol intake/day); smoking history (never, former, and
present smoker); body mass index (kg/m2 in
m2); usual daily hours of sun exposure during the
past year; history of actinic skin damage (self-reported
physician-diagnosed AK); and self-reported ability to tan after
prolonged sun exposure (no suntan, mildly tan, moderately tan, and
deeply tan). Inclusion of variables for fat intake, alcohol intake, and
smoking status did not alter any of the results and were excluded from
the final model. Age, sex, energy intake, inability to tan after
prolonged sun exposure, and history of diagnosed and treated AK were
included in the final multivariate models.

Tea consumption was defined by various methods. It was first assessed
by asking participants to self-define themselves as non-tea drinkers,
occasional drinkers, or regular tea drinkers. All occasional and
regular tea drinkers were then asked to report their usual consumption
of black tea, green tea, and herbal tea and for hot and iced tea
products. Average consumption for each tea product was categorized as
none, 1–3 cups/month, 1–6 cups/week, and ≥1 cup/day. Initial
analyses compared all tea drinkers to non-tea drinkers. Separate
analyses then compared various categories of hot and iced tea
consumption with non-tea drinkers. All statistical analyses were done
by using STATA computer software (Stata Corp. Stata statistical
software, intercooled stata, release 5.0, Stata Corporation, College
Station, TX).

Results

Population

A total of 270 men and 196 women who had participated in the
Southeastern Arizona Skin Cancer Study completed the tea consumption
questionnaire. Sixteen subjects reported drinking only herbal tea and
were excluded from the present analyses. The mean time between initial
interview and completion of the TQ was 2 years; whereas the mean time
between the TQ and SCC diagnosis was 2 years and 9 months. The
structure of the questionnaire allowed identification of subjects who
reported making recent changes in their tea consumption. Twenty-nine
subjects (16 cases and 13 controls) reported changes in the usual
amount of tea consumed from the lifetime consumption pattern. However,
only two subjects (one case and one control) reported that these
changes were made within the last 2 years. Exclusion of those 29
subjects from the analyses did not affect the results, so this report
includes data for all 450 subjects (234 cases and 216 controls).

Because the tea consumption questionnaire was completed in a subset of
the original participants, we compared subjects who participated in the
tea study (n = 466) with those who did not participate
(n = 329). We found no statistically significant
difference between the two groups in relation to case-control status,
gender, education, smoking, average hours per day in the sun in the
past year, and tanning ability. Participants in the tea study did
report more AK history than subjects who did not participate in the
study, with the increase being consistent for cases and controls.

Table 1⇓
shows the distribution of cases and controls according to sex, age,
education, reported tanning ability, history of AK, daily hours of sun
exposure during the past year, and smoking status. The study population
is an older, educated southwestern United States population with 68.8%
of cases and 66.2% of controls having some college education. There
was no difference between the cases and controls in the reported number
of hours spent in the sun. There was also no difference between cases
and controls in the number of years they have lived in Arizona. Only
tanning ability and history of AK showed a significant difference
between cases and controls (P < 0.001).

Pattern and Type of Tea Consumption and SCC Risk

In this Arizona population, 66.4% reported drinking tea during
the past year. Black tea was the predominant variety of tea consumed,
with 51.8% of all subjects reporting iced black tea drinking and
30.7% reporting hot black tea use. Only 8.7% of this population
reported drinking green tea. Overall, about 35% of women and 29% of
men reported drinking non-herbal tea regularly (here defined as
drinking tea at least once a week), whereas 27% of women and 38% of
men reported no tea drinking in the past year. Frequency of tea
consumption was not associated with smoking history or average daily
alcohol intake. Exclusive consumption of iced tea was slightly higher
in men and present smokers. There were no significant differences for
any of the risk factors listed in Table 1⇓
between subjects who reported
drinking only hot tea compared to those who reported drinking only iced
tea.

The association between usual pattern and type of tea consumed and risk
of skin SCC is presented in Table 2⇓
. In this analysis, usual tea consumption is defined as self-reported
non-tea drinker, occasional tea drinker, or regular tea drinker. There
was no association between either occasional or regular tea drinking
and risk of skin SCC. The associations between skin SCC and the
specific use of hot black tea or iced black tea are also presented in
Table 2⇓
. For black tea, controls were somewhat more likely to report
drinking hot tea compared to cases. The adjusted OR estimate for hot
tea intake was 0.63 (95% CI, 0.36–1.10). However, for iced tea, the
OR was 1.02 (95% CI, 0.64–1.63). Similar patterns were seen when
consumption was evaluated for winter or summer seasons separately (data
not shown). Green tea consumption was not common in this population.
Only 7.3% of cases and 10.2% of controls reported drinking hot green
tea, and 2.1% of cases and 1.9% of controls reported drinking iced
green tea. A suggestion of an inverse association was seen between
consumption of hot green tea (OR, 0.82; 95% CI, 0.35–1.90) and risk
of skin SCC. Decaffeinated tea consumption was not common in this
population. Only 6% of cases and 8.8% of controls reported drinking
decaffeinated hot tea, and 6% of cases and 5.1% of controls reported
decaffeinated iced tea use. Again, an inverse association was seen
between consumption of either regular hot tea (OR, 0.83; 95% CI,
0.46–1.48) or decaffeinated hot tea (OR, 0.83; 95% CI, 0.60–1.15)
and risk of skin SCC.

Estimated ORs and 95% CIs for the association between tea consumption
in the past year and skin SCC: SEAH-Tea Study

Tea Preparation Techniques and SCC

Because of potential differences in the association between hot
tea and iced tea and skin SCC risk, these two preparations were
evaluated separately.

Hot Black Tea.

Strength of tea was defined by the question “How do you usually drink
your tea,” with the categories recorded as “strong,”“
medium,” or “weak.” Table 3⇓
shows that controls were more likely to report drinking strong hot tea
than were the cases (OR, 0.74; 95% CI, 0.53–1.03). Strength of the
tea product was also evaluated using reported usual brewing time. There
was a significant correlation between reported brewing time and
reported strength of hot tea (r = 0.48;
P < 0.001). As shown in Table 3⇓
, controls were more
likely to report brewing hot tea for >3 min than were cases. There was
a significant trend between brewing time of hot tea and skin SCC
(P for trend = 0.03). Subjects were asked to identify
the preferred temperature for consumption of the hot tea (room
temperature, warm, hot, or very hot). Almost all subjects reported
drinking either hot (86.7%) or warm (9.6%) tea. There was a highly
significant correlation between reported usual temperature of hot tea
consumed and reported strength of hot tea (r = 0.94;
P < 0.001) as well as reported brewing time of hot tea
(r = 0.45; P < 0.001). Furthermore, a
significant inverse association was shown between the temperature of
hot tea and the risk of skin SCC (P = 0.05).

Estimated ORs and 95% CIs for the association between the strength,
brewing time, and temperature of the hot black tea consumed and skin
SCC: SEAH-Tea Study

We then evaluated the association between skin SCC and hot black tea
consumption by frequency of intake, adjusting for strength of the tea,
here measured as brewing time. The adjusted OR estimates for hot black
tea intake were 0.33 (95% CI, 0.12–0.87) for any hot tea drinking,
0.25 (95% CI, 0.07–0.84) for occasional use of 1–3 cups/month, and
0.57 (95% CI, 0.33–0.98) for regular use of ≥1 cup/week.

Iced Black Tea.

Table 4⇓
describes similar comparisons between skin SCC and various preparations
of iced tea consumption. Iced tea intake was categorized by strength of
prepared tea and by preparation techniques. Iced tea is prepared by
either brewing in hot water, or from instant tea, or as sun tea. Weak
statistically nonsignificant associations between iced tea consumption
and risk of SCC were observed for all tea preparation techniques and
strengths.

Estimated ORs and 95% CIs for the association between the strength and
preparation of the iced black tea consumed and skin SCC:
SEAH-Tea Study

Tea Consumption and Other Risk Factors for SCC Risk

The associations between hot and iced black tea intake and
skin SCC were evaluated for potential effect modification by selected
covariates (Table 5)⇓
. A statistically significant inverse association between hot black tea
consumption and the risk of skin SCC was observed among subjects in the
middle age-group (61–70 years old) category (OR, 0.07; 95% CI,
0.01–0.83). The pattern was similar for other age groups, although not
statistically significant. In addition, a statistically significant
inverse association between black hot tea consumption and skin SCC was
shown among nonsmokers (OR, 0.11; 95% CI, 0.02–0.68). Although hot
black tea consumption appeared to be generally inversely associated
with risk, there were no significant differences in the strata of any
of the other covariates. In contrast, iced tea consumption failed to
show any association with risk of skin SCC.

Discussion

This older Arizona population offered a unique opportunity
to study potential associations between consumption of tea and risk of
skin SCC. Arizona has one of the highest risks of skin SCC worldwide,
and tea is a commonly consumed beverage. In this population, two-thirds
reported drinking some tea during the past year, with more than half of
all subjects reporting iced black tea consumption and one third
reporting hot black tea use. In Arizona, iced tea was often prepared by
cooling brewed tea or by prolonged (6–15 h) steeping of tea in the sun
(sun tea). Over 37% of the study population reported consuming iced
tea as sun tea, and 24% consumed it from brewed iced tea. Cold
water-soluble instant teas, as well as tea beverages in a canned form,
were used by <10% of all tea drinkers. The remainder consumed a
mixture of either brewed iced tea or sun tea. Overall, we found no
evidence for a relationship between consumption of tea when broadly
defined as any use in the past year and skin SCC. However, we did find
evidence of an inverse association between the risk of skin SCC and
consumption of hot strong black tea.

In this study, we were able to estimate the ORs of skin SCC by
frequency and preparation habits, such as strength, brewing time,
preferred drinking temperature, and methods of preparation. The present
study shows that consumption of strong hot tea was inversely associated
with risk of skin SCC. This association was observed with multiple
definitions or markers of strong tea: reported strength of tea, brewing
time, and temperature. We were unable to detect a dose-response
reduction in skin SCC with increasing frequency of hot tea consumption.
This lack of dose-response might be explained by the fact that we did
not have adequate number of subjects reporting daily hot tea
consumption. Previous studies have shown that the tumor-inhibitory
effect of tea may depend on its intake level (2)
. For
example, at high concentrations, tea can effectively block endogenous
formation of N-nitroso compounds, whereas at low levels, it
may facilitate nitrosation reactions (18)
. In human
populations, the amount of tea polyphenols ingested is determined not
only by the frequency and amount of tea intake but also by the strength
of tea consumed. Tealeaf concentration and brewing time may be the most
important determinants of the polyphenol concentration in a cup of tea.

The difference in association with hot black tea consumption but not
iced black tea may be explained by the simple fact that iced tea is
likely to be consumed more diluted than hot tea. Iced tea is prepared
in larger amounts, using fewer tea bags. The usual recipe in Arizona
was 6–10 bags/gallon or 0.86–1.44 g of tea leaves/240 ml. In
contrast, regular hot tea is usually prepared by extracting one tea bag
per one cup (2.26 g/240 ml) of hot water. Another explanation might be
that the black tea flavonoids, theaflavins and thearubigins, form
insoluble complexes with caffeine, the so-called “tea cream,” when
tea is cooled (18, 19)
. These complexes precipitate in
cold water and remain in the bottom of the iced tea container.
Therefore, these complexes might not be ingested by iced tea drinkers,
reducing the intake of the active compounds. Instant tea is known to be
very low in tea flavonoids (20)
.

In some populations, tea drinking is associated with cigarette smoking
and alcohol drinking (21, 22)
. This was not the case in
our population, with the exception that iced tea consumption was
slightly higher in men and present smokers. Although adjustments were
made for these variables, the finding of a significant inverse
association of hot black tea consumption with skin SCC among nonsmokers
suggests that smoking may modify the effect of tea.

Some limitations and strengths of the study deserve consideration. In
case-control studies, the possibilities for recall and interviewer bias
are a major concern. Differential recall of diet and tea consumption
between cases and controls can lead to biased estimates of effect.
Furthermore, because there was a lag between diagnosis of the skin
cancer and interview, there is potential for cases to have altered
their behavior and to then report their recently changed behaviors.
Several steps were taken to reduce potential bias. Standard
questionnaires were administered to all subjects by a trained
interviewer who was not aware of the case-control status of the
subjects at the time of the TQ administration.

There is some evidence, however, that skin cancer cases did
recently alter their behavior for risk factors they thought were
related to skin cancer. For instance, they reported increased use of
sunscreens in the past year, whereas there were no differences between
cases and controls for sunscreen use during earlier time periods. They
also reported similar past year exposure to the sun to the controls.
Given that skin SCC is related to other measures of high UV exposure
(i.e., history of AK, history of sunburns), then the lack of
a finding for a differential sun exposure history for cases and
controls argues for a change in behavior since the diagnosis of the
skin cancer. However, although it appears that the cases did modify
some of their behaviors, there is no evidence that they recently
altered their consumption of tea products. In fact, because there have
been no prior studies of skin cancer occurrence and tea consumption, it
is unlikely that this population would have considered tea consumption
to be related to their risk of skin cancer. The difference in risk
patterns between consumption of iced tea and hot tea supports the lack
of differential recall between cases and controls in their reporting of
tea drinking. Public perception of tea drinking has been that there
would be no difference in the potential effect of tea based on
temperature. Furthermore, few participants reported recent changes
(within the past 2 years) in their tea drinking habits, and exclusion
of these did not alter the results of the study.

This is the first study to explore the relationships between different
tea consumption patterns, tea preparation techniques, and human cancer
of the skin. Although this study was of moderate sample size to explore
relationships within subgroups of tea consumption patterns, a
statistically significant inverse association between skin SCC and hot
black tea consumption was observed. Results show that tea concentration
(strength), brewing time, and beverage temperature influence the
potential protective effects of hot black tea in relation to skin SCC.
Further studies of increased sample sizes are needed to more completely
evaluate the interrelationships between preparation techniques, tea
type, and other life-style factors.

Acknowledgments

We thank Dr. David Alberts, director of the Division of Cancer
Prevention and Control, for his support; Steve Rodney for his
assistance with data management; and Mary Lurie for her assistance with
interviewing and data entry.

Footnotes

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.